After the Smoke Clears: Scars on the Immune System

Check out this article written in The Scientist by Danielle Gerhard, on the epigenetic marks of smoking on the immune system. A few quote from me in the piece:

“There is no human immune system; there is everyone's individual immune system,” said Adrian Liston, an immunologist at the University of Cambridge who was not involved in the study. “We really need to study things at the scale that the group in Paris is studying if we want to understand what's going to be relevant to human health at a population level.” 

That's TV Cambridge interview

My interview on Sensory Science for That's TV Cambridge.

Key point: Science is for everyone, the benefits of science are for everyone, so science communication needs to be for everyone.

Story time at the Cambridge Festival

Learning about vaccines and primary immunodeficiency through story! Maya's Marvellous Medicine and Battle Robots of the Blood, from our lab! Also available to read online.

VirusFighter

VirusFighter at the Cambridge Festival! The kids had a blast, maybe try it yourself? Want to be in the driving seat as UK Prime Minister during the COVID pandemic? Make real-time decisions based on the information available and watch the pandemic play out. Or maybe you are keen to genetically-engineer a virus to prevent the UK being overrun by invasive wombats? Give it a shot!

Diversity in the Immune System

In case you are interested in my public seminar on "Diversity in the Immune System" for the Cambridge Festival today, I've uploaded the talk. Only shame is that it misses the hour of interesting and insightful questions from the audience afterwards!

I was also interviewed about this talk:

What fascinates you most about the immune system?

 

That is not a fair question! There are so many aspects of the immune system that are simply amazing. The immune system is our most powerful sensory system – capable of detecting even single molecules and responding to them. It is also incredibly powerful – given the right signals, millions of immune cells can be rapidly recruited from the blood into a tissue, where they can coordinate an attack powerful enough to liquify it. Yet this incredibly sensitive and enormously strong immune system almost never gets it wrong. It lies dormant until we get an infection, then usually responds with the minimal force needed to eradicate that infection. As immunologists we study the allergies, autoimmune disorders and inflammatory conditions that happen when the immune system slightly misjudges, but really it is amazing that our immune system messes up as rarely as it does!

Why are some people susceptible to certain immune diseases and others aren’t? 

Diversity lies at the heart of immunity. The best defence against pathogens is diversity in responses from person to person. You can think of the immune system having a dozen different default settings, which influence how we will respond to different pathogens. Each of these settings have trade-offs, they make us a little more susceptible to some immune diseases and a lot more resistant to others. It keeps pathogens on their toes, makes it harder for them to adapt to human immune systems, precisely because there is no single default immune response. From an evolutionary perspective the cost-benefit of all of these settings was probably fairly equivalent, but of course times have changed. Now days most people probably don’t appreciate the advantage that their increased susceptibility to pollen allergy may give in fighting off parasitic worm infections that they rarely get exposed to! 

 What causes this diversity in the immune system?

Good question! The single biggest effect is our environment. The air we breathe, the food we eat, the chemicals we are exposed to, the bacteria that live inside us. These environmental exposures are probably responsible for half of all of the variation in immune responses from one person to another – it is even more important than genetics. One of the ways we can see this is by looking at the immune systems of couples that live together. After couples having been living together for a few years their immune systems seems to converge in their settings, becoming much more similar to each other. This is almost certainly due to sharing all of those environmental factors. Did you know that you transfer as many as 80 million bacteria in a single kiss? So even the bacteria that live in our gut become more similar when we live together.

How about sex and gender? 

Sex and gender are perhaps less important than you might think. Together they are responsible for maybe 5% of the variation you see in the immune system from person to person. Similar to the level of difference you see in a smoker versus a non-smoker. The most interesting aspect about this effect is that we really don’t know how much of the effect is sex and how much is gender. Biological sex certainly can modify our immune system, but gender is greatly under-estimated. A simple example of hidden gender effects is bladder cancer. 3 out of 4 bladder cancer patients are men, which is often described as a sex bias. However the underlying cause of most of these bladder cancers are exposures to chemicals such as aniline dyes, which were previously used in factories. So the high risk of bladder cancer in men is not due to biological differences between men and women, but rather due to the gendered segregation of jobs. The immune system is highly responsive to environmental exposures, and is certainly modified by gendered exposures (smoking, workplace pollutants, personal chemical exposures, etc). So how much of the “sex effect” is actually due to gender? The answer will vary a lot, because gender roles and exposures are constantly changing.

Is it possible to reprogramme someone’s immune system? 

For sure. Quit smoking, take up exercise, change your diet – all of these will reprogramme your immune system. The problem is just that we have very limited data on how these link back to what we really care about – our susceptibility to immune diseases. Ignore any claims about “immune boosting” on herbal supplements or “health” food products; the claims have no scientific basis, and the immune system does not work so simply. It is fair to say that certain foods and gut bacteria will likely push the immune system in one direction or another, and that these changes may be beneficial for different immune diseases. At some point in the (hopefully close) future, we may be able to advise simple diet changes to nudge someone back to health. Right now, though, anyone making claims like this is probably selling snake oil!

What are you working on at the moment?   

The one really reliable way to reprogramme your immune system is through vaccination! A vaccine gives your immune system a sneak peak to a future pathogen, letting it train up before the infection hits. Proven protection from that one infection, leaving the rest of the immune system dormant. There is incredible science behind vaccines; they are probably the single most consequential discovery in the history of medicine. But there is certainly room for improvement – some vaccines are great, others are merely good, and some populations (such as older people) don’t get all of the protection that we want them to have. So our work looking forward is to understand the diversity of immune responses to vaccines. We want to see if we can take the lessons from the people who respond to vaccines really well and use that information to improve the quality of vaccines for everyone else.

Sensory Science on the BBC

Cambridge University sensory-science art for people with sight loss

By Kate Bradbrook and Helen Burchell

BBC News, Cambridgeshire

Art exploring science and created for people with sight loss is on show as part of a festival organised by Cambridge University.

Sensory Science, at St Catharine's College, is part of the Cambridge Festival, which explores aspects of research carried out at the university and is open to the public.

Scientists at the Department of Pathology worked with local artists to create pieces to communicate science.

The festival runs until 28 March.

Sensory Science is the brainchild of Dr Erica Tandori, a low-vision artist based in Melbourne, Australia.

She was diagnosed with Stargardt disease - a form of macular dystrophy - when she was 23, and trained in creative arts and scientific communication.

"I'm an artist that's absolutely in love with science," she said.

"The whole idea of making things multi-sensory brings knowledge to life and makes it more accessible to everyone."

The pieces on show include lights and music and "is about all of us - cells and the immune system - and it should be available to all of us".

Together with Prof Jamie Rossjohn from Monash University in Australia, Dr Tandori saw the need for science communication to reach the blind and low-vision community.

She also worked with Prof Adrian Liston, professor of pathology at Cambridge University, who said: "The really unique aspect about this particular event is that we're really going for a multi-sensory approach.

"This involves not just the visual but auditory soundscapes, tactile maps, smell - other ways of communicating concepts.

"The aim is to make this as inclusive as possible.

"Using multiple senses is obviously a huge advantage if you want to include the blind and low-vision community."

Dr Julia Johnson, from Anglia Ruskin University, worked on the project with art and pathology students.

"We're looking at art's value in addressing some of the topics here," she said.

"We're thinking about how art can act as a communication tool for engaging audiences.

"Through a very sensory and tactile approach, young people and low-vision audiences can understand more about scientific models."

Read the article online here

Sensory Science

Liston-Dooley lab at the Cambridge Festival!

Our lab is gearing up for the Cambridge Festival! A lot of amazing activities, with something for everyone, so hopefully everyone in Cambridge can come and join at least one of these.

First of all, for our youngest visitors come along to a book reading of our kids books "Maya's Marvellous Medicine" and "Battle Robots of the Blood". We'll have some colouring in too, to keep them busy.

For kids a little older, Family Day at Pathology has a ton of activities! Our lab is hosting a display of "VirusFighter". See how your kids would have done as PM during the pandemic, or test whether they can successfully engineer a bioweapon to stop an invasion of wombats! (They can also play online now!)

 For all ages, we have a real treat, Sensory Science. This is a fantastic program that uses multi-sensory art to communicate the science of pathology. Honestly, everyone should come and experience this exhibit at St Catharine's College, the teams have put in so much work into their art piece. Our lab has coordinate the program and is exhibiting new art on neuroinflammation and cancer formation. We are also hosting the amazing Dr Erica Tandori, who started the Sensory Science movement back in Australia, and specialises in making science communication accessible to the blind and low vision community.

Finally, adults interested in the immune system are welcome to join my public seminar on how diversity shapes our immune responses!

Congratulations to Jasmine Hughes!

Congratulations to Jasmine Hughes for her Cook Society Award for dedicating herself to social justice, equality and strengthening the campus community, during her time at Duke University! I'm glad to say she is keeping up the focus during her PhD here at the University of Cambridge!

A looming threat to scientific publication

You can't argue with Professor John Tregoning, of Imperial College: these graphics are "objectively funny". 

But beyond the snickering, there is a reason why the biomedical science community is in uproar over this paper. 

It is a failure of peer review that this article was ever published in a scientific journal. Scientific articles are meant to be peer reviewed, precisely to catch garbage articles like this. No system is ever 100% perfect, and science is a rapidly-moving self-correcting ecosystem, but this is just so... prominant... a mistake, how did it happen?

To understand, it is important to recognise that scientists have been aware of the short-comings of peer review for years (and there are many!). The scientific publishing system is flawed: it is hard to find anyone that would argue against that. Unfortunately many of the "solutions" have made the problem worse.

"Open access publishing" opened up science to the world. Rather than "pay to read", scientists "pay to publish". On the plus side, the public can access scientific articles cost-free. On the down-side, it provided a market for pseudo-scientific journals, "predatory journals" to open up and accept any "scientific" article that someone is willing to pay to publish. One of the leading journals in the "open access" movement was "Frontiers". They genuinely transformed the style of peer review, making it rapid, interactive and very, very scaleable. Unfortunately the utopian vision of the journal clashed with the perverse economic incentives of an infinitely scaleable journal that makes thousands of dollars for every article it accepted. I was an early editor at the journal, and soon clashed with the publishing staff, who made it next-to-impossible to reject junk articles. I resigned from the journal 10 years ago, because the path they were taking was a journey to publishing nonsense for cash.

Fast-forward 10 years, and Frontiers publishes more articles than all society journals put together. Frontiers in Immunology publishes ~10,000 articles a year; as a reference, reputable society journals such as Immunology & Cell Biology publish ~100 papers a year. Considering Frontiers earns ~$3000 per article, it is a massive profit-making machine. The vision of transforming science publishing is gone, replaced with growth at all costs. Add onto this a huge incentive to publish papers, even ones that no one reads, and it added to a perverse economy, with "paper mills" being paid to write fake papers and predatory journals being paid to publish them, all to fill up a CV.

Generative AI turbo-charges this mess. Some basic competency at using generative AI, and scamming scientists can rapidly fake a paper. This is where #ratdckgate comes in. The paper is obviously faked, text and figures. Yet it got published. A lot of failures in the system here, in particular perverse incentives to cheat, the generation of an efficient marketplace for cheating, and a journal that over-rode the peer reviewers because it wanted the publication costs. 

As the Telegraph reports, this is "a cock up on a massive scale".

No one really cares about this article, one way or another. Frontiers has withdrawn the article, and even congratulated itself on its rapid action for the one fake paper that went viral, without dealing with the ecosystem it has created. The reason why the scientific community cares is that this paper is just the tip of the iceberg. The scientific publishing system was designed to catch good-faith mistakes. It wasn't designed to catch fraud, and isn't really suitable for that purpose. Yes, reviewers and editors look out for fraud, but as generative AI advances it will be harder and harder to catch it, even at decent journals. It is an arms race that we can't win, and many in the scientific publishing world are struggling to see a solution.

There are many lessons to be learned here:

• The scientific career pathway provides perverse incentives to cheat. That is human nature, but we need to change research culture to minimise it
• Even good-intentions can create toxic outcomes, such as open access creating the pay-to-publish market place. We need to redesign scientific publishing fully aware of the way it may be gamed, and pre-empt toxic outcomes
• Peer review isn't perfect, and isn't even particularly good at catching deliberate fraud. We probably need to separate peer-review from fraud detection, and take a seperate approach to each
• Scientific journals range radically in the quality of peer review. We need a rigorous accreditation system to provide the stick to publish journals that harm science
• Generative AI has huge potential for harm, and we need to actively design systems to mitigate those harms

Improving scientific publishing is a challenge for all of us. In a world where science is undermined by politics, we cannot afford to provide the ammunition to vaccine deniers, climate change deniers, science skeptics and others who want to discredit science for their own agenda. So we need to get our house in order.